The central purpose of this proposal is to define further the metabolism of lead in children. Since bone is the organ of greatest lead accumulation, the primary focus is to characterize in detail the metabolism of the rapidly exchangeable lead compartment loosely bound to bone, under "steady state" conditions and during lead chelation by EDTA and D-pencillamine. The major phase of the research plan will be carried out in bone organ culture, a technique that has provided, in many instances, the link between in vivo observations and those made at the molecular level. Companion in vitro studies will examine: 1) the role of rat calcium-binding activity and chick calcium-binding protein on the intestinal absorption of lead, and 2) the effects of the calcium ionophore, A23187, on mechanisms of lead transport from red cell to plasma. Clinical research in lead intoxicated children will examine the role of metal-metal-hormone interactions during chelation therapy; and a supplementary nutritional program will be carried out in children with "low level lead toxicity." This comprehensive research plan, with emphasis on metal-metal-hormone interactions, should help to define further the hormonal and ionic regulators of bone lead metabolism and mechanisms of lead transport. As a result, the metabolic hazards of "low level lead toxicity" may be understood and more effective treatment for childhood lead intoxication may evolve.